High pressure, low flow rate fluid flow control

ABSTRACT

An adjustable high pressure, low flow metering valve provides a sleeve extending about a restrictor shaft, the sleeve having a narrow helical groove formed in the inside diameter. A restrictor shaft within the sleeve encloses the groove and forms a sealed helical flow channel. The length of the flow channel is varied by withdrawing the restrictor shaft in the sleeve, whereby only a selected axial extent of the groove is enclosed by the sleeve to form a confined flow path. The shaft is provided with a threaded engagement in the body of the metering valve, so that rotation of an adjustment knob provides extremely fine control of the length of the flow path, and thus highly accurate selection of the flow resistance.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] Not applicable.

FEDERALLY SPONSORED RESEARCH

[0002] Not applicable.

SEQUENCE LISTING, ETC ON CD

[0003] Not applicable.

BACKGROUND OF THE INVENTION

[0004] 1. Field of the Invention

[0005] The present invention relates to fluid flow control, and, moreparticularly, to an improved method and apparatus to generate extremelylow flow rates at high pressures that are accurately regulated for usein liquid chromatography and mass spectrometry.

[0006] 2. Description of Related Art

[0007] In liquid chromatography, the liquid (solvent) flow ratesgenerally used are between 100 μliters/min and 10 ml/min. However, morewidespread use of capillary and micro-bore columns, as well as newapplications such as combining liquid chromatography with massspectrometry has created a requirement for flow rates that are as muchas 100 times lower than the above mentioned flow rates. Very few HPLCpumps are capable of delivering accurate, stable flow rates in thisrange, and those that can do so are extremely expensive. As a result,most manufacturers have adopted a method known as flow splitting toachieve low flow rates with conventional high pressure liquidchromatography pumps. In the prior art, flow splitting is accomplishedby using a tee to split the flow into two paths. Capillary tubes ofdifferent lengths and/or diameters are used on each path to createdifferent fluid resistance in each path. Because these flow rates areall in the laminar flow regime, the resulting flow rates in each pathcan be found from the following relation:${\Delta \quad P} = \frac{\mu \quad {LQ}}{d^{4}}$

[0008] where P is pressure, μ is dynamic viscosity, L is capillary flowlength, Q is flow rate, and d is effective capillary diameter.

[0009] The significant disadvantages of prior art include:

[0010] Capillary tube is easy to clog.

[0011] Split ratios may change during a chromatographic run because ofchanges in fluid viscosity that occur during the run. This may occurbecause the volume in the capillary tubing can be large enough that thecomposition of solvents can become different in the two legs when thepre-split composition is changing.

[0012] Difficult to adjust split flow ratio. It is necessary to cut thetubing to different lengths to adjust the split ratio. This is difficultto do because the capillary usually closes off due to crimping in thecutting process available to most chromatographers in the lab, and thusthe fluid resistance changes unpredictably. Also, it is necessary to cutand join additional pieces of tubing to add resistance. This is atroublesome and time consuming process because of the small tube andfitting size.

[0013] Verifying the flow rate is extremely difficult. There are nocommercially available flow meters that work at these low flow rates.Measuring flow rates as low as 100 nanoliters per minute must be done byweighing the effluent on the low path side over a known time interval.This is very time intensive. Using traditional methods, such as pressuredrop through a known capillary, do not work because the viscosity of thefluids is often changing over time, and is unknown.

[0014] When the capillary analytical column is added to the low flowpath, the split ratio is changed. The resistance of analytical columnsis usually unknown, and will change with a change in solvent viscosity.Thus, it is necessary for the user to measure flow rates after addingthe column to the flow splitter.

BRIEF SUMMARY OF THE INVENTION

[0015] The present invention generally comprises a method and apparatusfor controlling and regulating the high pressure, low flow systems usedin HPLC and the like.

[0016] A major aspect of the invention is the design of an adjustablehigh pressure, low flow metering valve. Other prior art devices haveattempted to use orifice metering. This approach works well at high flowrates, but is unstable at these low flows and high pressures. Even achange in diameter of one millionth of an inch in the orifice diameterwill produce an unacceptable change in back pressure. The presentinvention provides a sleeve that extends about a restrictor shaft, thesleeve having a narrow helical groove formed in the inside diameterthereof. A restrictor shaft is disposed within the sleeve in a press fitto enclose the groove and form a sealed helical flow channel thatapproximates a very small diameter capillary with a rather long pathlength. The long path tends to negate variations in effective diameterover the length of the flow path. The adjustment in fluid resistance ismade by adjusting the length of the flow path. This is accomplished bychanging the length of engagement of the restrictor shaft with thehelical flow path created between the shaft and the bore. The length ofthe flow channel is varied by withdrawing the restrictor shaft in thesleeve, whereby only a selected axial extent of the groove is enclosedby the sleeve to form a confined flow path. The shaft is provided with athreaded engagement in the body of the metering valve, so that rotationof an adjustment knob provides extremely fine control of the length ofthe flow path, and thus highly accurate selection of the flowresistance.

[0017] The flow path is a groove having a 60° triangular cross-sectionwhich is provided to resist clogging. This groove has a flow resistanceapproximately the same as a tubular path having a diameter that fitswithin the 60° triangle, yet the triangular configuration permits thepassage of particulates larger than the diameter of the tubular path.

[0018] Changes in the effective diameter that might otherwise be createdby the engagement of the shaft and bore are minimized by creating apress fit of the shaft in the sleeve that induces compressive stresslevels higher than the maximum operating pressure (5000 psi), and yetwhich are below the stress level at which long term creep is significant(as determined by the so-called 1000 hour modulus of the outer tubematerial). Furthermore, the adjustable device is inherentlyself-cleaning: contamination in the flow path is flushed out when therestrictor shaft is retracted and the groove is exposed.

[0019] A further aspect of the invention is a method and apparatus foran adjustable metering valve. Placing a fixed fluid resistor element onthe low flow path, and a variable fluid resistor (adjustable meteringvalve) on a parallel, high flow rate path, the chromatographer canadjust the split flow ratio to virtually any ratio desired. For example,if the user requires nanoliter flow rates, a high fixed resistancecartridge is selected for the low flow rate path that provides areasonable back pressure at the desired flow rate (say 1000 psi at 100nanoliters per minute—it is important not to exceed the maximum orminimum pressure limits of the pump). Then the exact desired flow ratethrough the low flow path is obtained by means of the adjustableresistance valve in the high flow path. When the metering valve isadjusted to 1000 psi back pressure, the resistor chosen in this examplewill provide exactly 100 nanoliters per minute of flow. Because thevolume in the fixed resistor and adjustable resistance valve isnegligible compared to the flow rate and residence time in eachrespective path, the solvent composition and viscosity differences ineach path are negligible (less than 1%).

[0020] Another aspect of the invention is a flow meter that can measurethe flow rates on both pathways. A high pressure pump feeds a parallelcircuit layout, one branch having fixed resistance, a pressuretransducer, and an HPLC analytical column. The other branch includes afixed resistance, another pressure transducer, and the adjustableresistance valve. Because flow rates are laminar, the flow rate can bedetermined by measuring the pressure drop across the two fluid resistorelements. The flow meter also allows for the user to know what flow rateis passing through the analytical column without needing to know theresistance of the column. The flow meter also provides a means todocument the flow rate during the chromatographic run. This is veryimportant for validating results in drug testing or other criticalapplications.

[0021] Accuracy of measurement is not affected by solvent gradient runs.Because the resistor elements each have negligible volume (below 50nanoliters) the residence time of solvents in each path is too small topermit sufficient change in fluid viscosity to alter measurementaccuracy.

[0022] Another aspect of the invention is the ability to gang multiplecontroller/meter units together to achieve multi-channel flow splitting.The mass spectrometers that are used with HPLC's are capable of doinganalyses in much less time than the HPLC. So, when combining the outputof HPLC to LC-MS, the LC-MS must sit idle while the HPLC completes arun. This is a problem because the mass spectrometer systems typicallycost 10 times as much as an HPLC pump and column. Prior art devices usemultiple pumps working simultaneously to feed samples through multiplecolumns for sample separation, and then into the mass spectrometer forfinal analyses (the mass spec is multiplexed). The present inventionallows a single HPLC pump to split flow multiple ways into multiplebranches, and then into the mass spectrometer. Each branch includes apressure transducer, a signal conditioner, and an ADC feeding a digitalcomputing device. The computing device also controls an actuator driverthat operates a servo device to selectively vary the variable resistancevalve described above. This arrangement provides a great cost savings aswell as an important improvement in overall system reliability (an 8channel system would normally have 32 check valves, 16 high pressureseals, and is very prone to down time).

BRIEF DESCRIPTION OF THE DRAWING

[0023]FIG. 1 is a cross-sectional view of the adjustable flow resistancevalve of the present invention, shown in the maximum flow resistancedisposition.

[0024]FIG. 2 is a cross-sectional view of the adjustable flow resistancevalve of FIG. 1, shown in a reduced flow resistance disposition.

[0025]FIG. 3 is a schematic diagram of the flow metering circuit of thepresent invention.

[0026]FIG. 4 is a magnified cross-sectional view of the triangulargroove flow path of the adjustable flow resistance valve of theinvention.

[0027]FIG. 5 is a functional block diagram of a multi-channel flowsplitting arrangement for a plurality of ganged flow metering circuits.

DETAILED DESCRIPTION OF THE INVENTION

[0028] The present invention generally comprises a method and apparatusfor controlling and regulating the high pressure, low flow systems usedin HPLC and the like. With regard to FIG. 1, a major aspect of theinvention comprises an adjustable flow rate valve 11 for such highpressure, low flow systems. The valve 11 includes a valve body 12 havinga stepped bore 13 extending generally axially therethrough. A sleeve 14of stainless steel or the like is secured within the bore 13, and ahelical groove 16 is formed in the inner circumferential surface of thesleeve. The axial extent of the helical groove 16 (shown in breakaway inFIG. 1) is substantially the entire length of the sleeve. A restrictorshaft 17 is press fit into the sleeve 14, the outer surface of the shaft17 impinging on the inner circumferential surface of the sleeve andsealing the helical groove 16 to define an enclosed helical capillaryfluid flow path through the groove 16. The length of the flow path maybe many times larger than the length of the sleeve 14, and the long pathtends to negate any variations in effective diameter over the length ofthe flow path. An extension 18 of the shaft 17 extends outwardlytherefrom, and is provided with indicia that indicate a liquid flowratio, as will be described in the following. High pressure sealassemblies 19 and 21 are secured at opposed ends of the sleeve 14 tocontain the high pressure liquid fed through the device.

[0029] A high pressure input fitting 22 is secured in the valve body 12,and is connected through a small passage 23 to a flow space at the innerend of the helical groove 16. Another high pressure input fitting 26 issecured to the body 12, and a fixed flow resistance cartridge 27 isincorporated within the fitting 26. The fitting 26 communicates throughpassage 24 to the flow space at the inner end of the groove 16. Thisarrangement permits high pressure liquid to be input through fitting 22,the liquid flow being split so that some of the flow proceeds throughgroove 16 and the remainder of the flow goes through passage 26 andfixed flow resistance 27 to a low flow output branch, as will bedescribed further below.

[0030] The fluid resistance of the flow path through groove 16 isselected by adjusting the length of the flow path. This is accomplishedby changing the length of engagement of the restrictor shaft 17 with thehelical flow path 16. Secured to body 12 is a valve body extension 42,which includes a central bore 43 aligned with bore 13. Restrictor shaft17 includes a head 44 that is secured within a drive block 46, and block46 is axially translatable within bore 43. Block 46 is provided with alongitudinally extending groove 47, and pin 48 extends from component 42to the groove 47 to prevent rotation of block 46. Shaft 49 extendsaxially from block 46, and is provided with fine drive threads

[0031] A cap assembly 52 is secured coaxially to the extension 42, andsupports a rotatable collar 53 that has internal threads adapted toengage drive threads 51. Adjustment knob 54 is secured about the capassembly 52, and pin 56 joins the knob to the collar 53 for rotation incommon. Thus the knob may be rotated to turn the collar 53 so that thethreads 51 move the drive block axially and translate the restrictorshaft axially. FIG. 2 depicts the device 11 with the restrictor shaft 17translated partially outwardly (to the right in FIG. 2) so that aportion of the helical groove 16 is unsealed, reducing the length of thecapillary flow path so that the fluid flow resistance is reducedconcomitantly. It may be appreciated that the knob 54 may be replaced bya motorized rotational drive, such as a stepper motor, for automatedflow adjustment.

[0032] The restrictor shaft 17 is preferably formed of a ceramicmaterial so that the press fit thereof into the sleeve 14 does notcreate spalling or other surface disruptions that could introducecontamination and particulate debris into the flow stream.

[0033] The fixed fluid flow resistance 17 may comprise any convenientconstruction known in the prior art. One preferred embodiment maycomprise a helical groove formed in the receptacle that receives thecartridge 27, the cartridge 27 serving to seal the helical groove andform a helical capillary flow path in a fashion similar to thecomponents 14, 16, and 17, although the non-movable cartridge 27 definesa fixed, non-adjustable flow path having a fixed resistance. A number offittings 26 may be provided, each having a cartridge 27 with a differentknown fluid flow resistance, whereby fittings 26 may be interchanged toselectively modify the fixed resistance and the low flow output.

[0034] With regard to FIG. 4, the groove 16 in the sleeve 14 is definedby a 60° equilateral triangle. The groove has a flow resistanceapproximately the same as a capillary tube 61 having a diameter thatfits within the 60° triangle, yet the triangular configuration has theadvantage of permitting the passage of particulates, such as oblongparticle 62, that are larger than the diameter of the tubular capillary61. Thus clogging of the flow path is minimized. The hydraulic radius ofa triangular groove is given by the relationship:

Hydraulic radius=^((cross sectional area))/_((wetted perimeter))

Area of triangular groove=^(Base×Height)/₂

Wetted perimeter=3×Base

Hydraulic radius=h/6

[0035] The equivalent diameter of a circular groove=4×hydraulic radiusor 2h/3. A conduit of circular cross section h would provide the samepressure drop as a 60° triangular groove of depth=1.5h. Therefore, sincemost particles have irregular shapes, there is less chance for cloggingto occur in the 60° triangular groove.

[0036] Another salient feature of the invention is a flow meter that canbe employed to adjust and measure the flow rates in a HPLC arrangement.With regard to FIG. 3, a high pressure pump 63 delivers a flow Q to twoparallel branches 64 and 66. Branch 64, a low flow path, is comprised ofa fluid resistance R₁ having a flow q₁ therethrough and a pressure dropP₁, which is connected to the analytical column having an unknown flowresistance R_(c). Branch 66, a high flow path, is comprised of a fluidresistance R₂ having a flow q₂ therethrough and a pressure drop P₂,which is connected to the adjustable flow resistance R_(v) of the device11 described above. R₁ may comprise the fixed, known flow resistance ofcartridge 27 of the device 11. The following relationships pertain tothe calculation of flow rate through the column: $\begin{matrix}{Q = {q_{1} + q_{2}}} \\{q_{1} = \frac{\left( {P - P_{1}} \right)}{\mu \quad R_{1}}} \\{q_{2} = \frac{\left( {P - P_{2}} \right)}{\mu \quad R_{2}}} \\{q_{1} = \frac{{R_{2}\left( {P - P_{2}} \right)}Q}{{R_{1}\left( {P - P_{2}} \right)} + {R_{2}\left( {P - P_{1}} \right)}}}\end{matrix}$

[0037] It is apparent that viscosity is not a factor in calculating theflow rates, and a process monitoring device may be easily programmed tocalculate the flow rates in real time based on measured parameters P, P₁and P₂. The flow meter also allows for the user to know what flow rateis passing through the analytical column without needing to know theresistance of the column. The flow meter also provides a means todocument the flow rate during a chromatographic run.

[0038] Another salient feature of the present invention is that itallows a single HPLC pump to split flow multiple ways into multiplebranches, and then into the mass spectrometer. With regard to FIG. 5,each branch includes a pressure transducer 71, a signal conditioner 72,and an A/D converter 73 feeding a digital computing device 74. Thecomputing device 74 is programmed to control an actuator driver 76 thatoperates a servo device 77 (such as a stepper motor) to selectively varythe variable resistance valve 11 described above. A status display 78and an interface 79 to an external computer for data collection andmonitoring may also be provided. This arrangement provides a great costsavings as well as an important improvement in overall systemreliability.

[0039] The foregoing description of the preferred embodiment of theinvention has been presented for purposes of illustration anddescription. It is not intended to be exhaustive or to limit theinvention to the precise form disclosed, and many modifications andvariations are possible in light of the above teaching without deviatingfrom the spirit and the scope of the invention. The embodiment describedis selected to best explain the principles of the invention and itspractical application to thereby enable others skilled in the art tobest utilize the invention in various embodiments and with variousmodifications as suited to the particular purpose contemplated. It isintended that the scope of the invention be defined by the claimsappended hereto.

1. An adjustable resistance device for high pressure, low flow rateliquids, including: a sleeve having an internal surface; a grooveextending into said internal surface of said sleeve; a restrictor shaftdisposed within said sleeve, said restrictor shaft having an outercircumferential surface impinging on said internal surface of saidsleeve and forming a seal with said groove to define a flow path withinsaid groove; means for translating said restrictor shaft within saidsleeve to selectively unseal portions of said groove and change thelength of said flow path within said groove.
 2. The adjustableresistance device of claim 1, wherein said sleeve is a tubular member.3. The adjustable resistance device of claim 2, wherein said grooveextends generally helically in said internal surface.
 4. The adjustableresistance device of claim 1, wherein said restrictor shaft is press fitinto said sleeve.
 5. The adjustable resistance device of claim 1,wherein said restrictor shaft is formed of a ceramic material.
 6. Theadjustable resistance device of claim 1, wherein said means fortranslating includes threaded means connected to one end of saidrestrictor shaft.
 7. The adjustable resistance device of claim 6,further including means for preventing rotation of said restrictor shaftwhile permitting axial translation of said restrictor shaft.
 8. Theadjustable resistance device of claim 6, wherein said threaded meansincludes a threaded drive shaft connected to said restrictor shaft, andfurther including a rotatable collar connected to said sleeve, saidcollar having internal threads to engage said threaded drive shaft. 9.The adjustable resistance device of claim 8, further including a manualadjustment knob connected to said rotatable collar.
 10. The adjustableresistance device of claim 8, further including motor drive means forrotating said rotatable collar.
 11. The adjustable resistance device ofclaim 1, further including a sealed first flow space disposed at a firstend of said groove.
 12. The adjustable resistance device of claim 11,further including a high pressure input fitting connected to said firstflow space.
 13. The adjustable resistance device of claim 12, furtherincluding a low flow output fitting connected to said first flow space.14. The adjustable resistance device of claim 13, wherein said low flowoutput fitting includes a fixed fluid resistance therein.
 15. Theadjustable resistance device of claim 14, further including a pluralityof interchangeable low flow output fittings, each having a differentfixed fluid resistance.
 16. The adjustable resistance device of claim11, further including a sealed second flow space disposed at a secondend of said groove.
 17. The adjustable resistance device of claim 16,further including a high flow output fitting connected to said secondflow space.
 18. The adjustable resistance device of claim 14, furtherincluding a sealed second flow space disposed at a second end of saidgroove, a high flow output fitting connected to said second flow space,said fixed fluid resistance having a flow resistance greater than theflow resistance of said flow path through said groove.
 19. Theadjustable resistance device of claim 18, further including an indicatorshaft extending outwardly from said restrictor shaft to indicate theratio of flow rate through said fixed flow resistance compared to flowrate through said flow path.
 20. A fluid flow meter arrangement,including: a high pressure fluid source connected to first and secondparallel flow paths; said first flow path having a known fixed flowresistance connected in series to a first pressure sensor and thence toan unknown flow resistance; said second flow path having a second fixedflow resistance in series with a second pressure sensor and anadjustable fluid flow resistance.
 21. The fluid flow meter arrangementof claim 20, wherein said pressure sensors generate pressure signals,and means for digitally computing flow rates through said first andsecond flow paths.
 22. The fluid flow meter arrangement of claim 21,wherein said means for digitally computing includes a signal conditionand A/D converter connected to each pressure sensor.
 23. The fluid flowmeter arrangement of claim 22, wherein said means for digitallycomputing includes servo means for automatically varying said adjustablefluid flow resistance in response to said computed flow rates.